CENTER FOR DRUG EVALUATION AND
`RESEARCH
`
`
`APPLICATION NUMBER:
`
`204063Orig1s000
`
`PROPRIETARY NAME REVIEW(S)
`
`
`
`
`
`

`

`
`
`Department of Health and Human Services
`Public Health Service
`Food and Drug Administration
`Center for Drug Evaluation and Research
`Office of Surveillance and Epidemiology
`Office of Medication Error Prevention and Risk Management
`
`Proprietary Name Review
`
`Date:
`
`January 16, 2013
`
`Julie Neshiewat, PharmD
`Reviewer:
`Division of Medication Error Prevention and Analysis
`
`Irene Z. Chan, PharmD, BCPS
`Team Leader:
`Division of Medication Error Prevention and Analysis
`
`Carol Holquist, RPh
`Division Director:
`Division of Medication Error Prevention and Analysis
`
`Drug Name and Strengths: Tecfidera (Dimethyl Fumarate) Delayed-release Capsules
`120 mg and 240 mg
`
`
`
`
`Application Type/Number: NDA 204063
`Applicant/Sponsor:
`Biogen Idec
`OSE RCM #:
`2012-2508
`*** This document contains proprietary and confidential information that should not be
`released to the public.***
`
`
`
`
`
`
`
`Reference ID: 3246593
`
`

`

`
`
`CONTENTS
`
`1
`
`INTRODUCTION................................................................................................................... 1
`1.1
`Regulatory History......................................................................................................... 1
`1.2
`Product Information ....................................................................................................... 1
`2 RESULTS................................................................................................................................ 2
`2.1
`Promotional Assessment................................................................................................ 2
`2.2
`Safety Assessment.......................................................................................................... 2
`3 CONCLUSIONS ..................................................................................................................... 6
`3.1
`Comments to the Applicant............................................................................................ 6
`4 REFERENCES........................................................................................................................ 7
`APPENDICES............................................................................................................................... 10
`
`
`
`
`
`
`Reference ID: 3246593
`
`

`

`1
`
`INTRODUCTION
`
`This review evaluates the proposed proprietary name, Tecfidera, from a safety and
`promotional perspective. The sources and methods used to evaluate the proposed name
`are ouflined in the reference section and Appendix A respectively.
`
`1.1
`
`REGULATORY HISTORY
`
`Dimethyl flunarate is a New Molecular Entity (NME . This roduct was reviewed under
`IND 073061 with the proposed proprietary name,
`, which was found
`
`NDA 204063. In OSE Review # 2012-542 dated Ma 23, 2012, DMEPA oun
`
`
`28I 2010. The Applicant
`acceptable in OSE Review # 2009—2403 datedAi
`subsequently requested to withdraw the name,
`and requested review of the
`proposed proprietary name,_ In OSE Rev1ew # 2010-2674 dated May 26,
`
`2011, the Division of Medication Error Prevention and Anal sis MEPA found the
`
`
`name unacc
`table
`
`
`
`. OnFe
`29, 2012, eA cant
`
`
`submittedarequestforthereviewoftheproposedproprietaryname,*under
`
`
`
` In OSE Review # 2012-1263, DMEPA found
`
`proposed proprietary name,
`the name unacc
`table
`
`On August 29, 2012, the
`A licant submitted a request for the review of the proposed proprietary name,
`
`On October 19, 2012, the OSE Pro'ect Mana er e-mailed the A licant
`roduc
`
`statin that DMEPA 1dent1fied a fore1
`
`
`2012, the Applicant withdrew the proposed proprietary name
`On October 24, 2012, the Applicant submitted a request for the review of the proposed
`proprietary name, Tecfidera.
`
`e name
`
`The labels and labeling for Dimethyl Fumarate were reviewed under separate cover (OSE
`Review # 2012-530).
`
`1.2
`
`PRODUCT INFORMATION
`
`The following product information is provided in the October 24, 2012 proprietary name
`submission.
`
`0 Active Ingredient: Dimethyl Fumarate
`
`0
`
`Indication of Use: Treatment of atients with rela s' multi 1e sclerosis
`
`”Ilisdoummnimpmpkmymdmfidmfiflhfimnfimfinshmfldmbemhsedmfiemlbfic.
`
`Reference ID: 3246593
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`1
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`

`

`0 Route of Administration: Oral
`
`I Dosage Form: Delayed-release capsules
`
`0
`
`Strength: 120 mg, 240 mg
`
`0 Dose and Frequency: 120 mg by mouth twice daily for 7 days, then 240 mg by
`mouth twice daily; temporary dose reduction to 120 mg twice daily may reduce
`occurrence of flushing and GI side effects — within 1 month, the recommended
`dose of 240 mg twice daily should be resumed
`
`0 How Supplied:
`0
`
`(II)(4)
`
`o 30 day starter pack (l4—count bottle 120 mg capsules and 46-count bottle
`240 mg capsules packaged in the same carton): retail and professional
`sample
`0 120 mg capsules
`I
`14-count bottle: retail and professional sample
`0 240 mg capsules
`I
`14-count bottle: retail and professional sample
`I
`60—count bottle: retail
`
`0
`
`Storage: Store at 15°C to 30 °C (59°F to 86 °F). Protect capsules from light;
`Once opened, discard bottles after 90 days
`
`0 Container and Closure Systems: HDPE bottles sealed with an aluminum foil
`induction seal and white polypropylene
`(w)
`
`2 RESULTS
`
`The following sections provide the information obtained and considered in the overall
`evaluation of the proposed proprietary name.
`
`2.1
`
`PROMOTIONAL ASSESSMENT
`
`The Office of Prescription Drug Promotion (OPDP) determined the proposed name is
`acceptable from a promotional perspective. DMEPA and the Division of Neurology
`Products (DNP) concurred with the findings of OPDP’s promotional assessment of the
`proposed name.
`
`2.2
`
`SAFETY ASSESSMENT
`
`The following aspects were considered in the safety evaluation of the name.
`
`2.2.1 United States Adopted Names (USAN) SEARCH
`
`The November 28, 2012 search of the United States Adopted Name (USAN) stems did
`not identify that a USAN stem is present in the proposed proprietary name.
`
`Reference ID: 3246593
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`2
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`

`2.2.2 Components ofthe Proposed Proprietary Name
`
`The Applicant indicated in their submission that the proposed name, Tecfidera, has no
`derivation or intended meaning. This proprietary name is comprised of a single word that
`does not contain any components (i.e. a modifier, route of administration, dosage form,
`etc.) that are misleading or can contribute to medication error. Since Tecfidera is a
`delayed—release capsule, we evaluated whether or not the proposed name requires a
`modifier to signal the delayed—release nature of the product (see Failure Mode and Effects
`Analysis of Modifier — Section 2.2.6).
`
`2.2.3 FDA Name Simulation Studies
`
`Eighty-four practitioners participated in DMEPA’s prescription studies. The
`interpretations did not overlap with any currently marketed products, but the verbal
`prescription interpretation “Taxadera” sounds similar to “Taxotere,” which was identified
`during the Expert Panel Discussion (EPD) as an orthographically similar name to
`Tecfidera. Due to similarity in speech, Taxotere was evaluated as an orthographically
`similar and phonetically similar name to Tecfidera in Appendix E. A comment was
`received from one of the participants that the written prescription reminded her of
`Terbinafine 250 mg. Terbinafme was evaluated as an orthographically similar name to
`Tecfidera in Appendix E. The written prescription studies show that the first letter ‘T’
`can be misinterpreted as a ‘J,’ ‘F,’ or ‘L.’ The verbal prescription studies show that the
`infix ‘0? can be misheard as an ‘x.’ These written and verbal misinterpretations of letters
`and syllables of the name, Tecfidera, were evaluated. See Appendix C for the complete
`listing of interpretations from the verbal and written prescription studies.
`
`2.2.4 Comments from Other Review Disciplines
`
`In response to the OSE, November 27, 2012 e—mail, the Division of Neurology Products
`(DNP) did not forward any comments or concerns relating to the proposed name at the
`initial phase of the proprietary name review.
`
`2.2.5 Failure Mode and Effects Analysis ofSimilar Names
`
`Appendix B lists possible orthographic and phonetic misinterpretations of the letters
`appearing in the proposed proprietary name, Tecfidera. Table 1 lists the names with
`orthographic, phonetic, or spelling similarity to the proposed proprietary name, Tecfidera,
`identified by the Primary Reviewer (PR) and the Expert Panel Discussion (EPD). Table
`1 also includes the name, Terbinafine, which was identified from a comment in the FDA
`Name Simulation Study that was not identified by DMEPA and required finther
`evaluation.
`
`Table l: Collective List of Potentially Similar Names (PR, EPD, FDA)
`
`Look Similar
`
`Name
`
`Source
`
`Name
`
`Source
`
`Name
`
`Source
`
`Benefiber
`
`EPD
`
`Faslodex
`
`EPD
`
`Taclonex
`
`EPD
`
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`

`Table 1: Collective List of Potentially Similar Names (PR, EPD, FDA)
`
`Look Similar
`
`Name
`
`Source
`
`Name
`
`Source
`
`Name
`
`Source
`
`Decitabine
`
`EPD
`
`Jentadueto
`
`Famotidine
`
`EPD
`
`Lidodenn
`
`EPD
`
`EPD
`
`Lofibra
`
`EPD
`
`Actidose with PR
`
`Sorbitol and
`Actidose-
`
`Aqua
`
`Trabedersen
`
`PR
`
`Terbinafme
`
`FDA
`
`Taladine
`
`Teflaro
`
`EPD
`
`EPD
`
`Tektuma
`
`EPD
`
`EPD
`
`EPD
`
`PR
`
`EPD
`
`EPD
`
`Lubridenn
`
`PR
`
`Ticlodipine
`
`Lobeline
`
`Istodax
`
`EPD
`
`EPD
`
`Zorbtive
`
`Rebif
`
`Rebidose‘”
`
`Bifidus
`
`PR
`
`Lidodan
`
`Lactulose
`
`EPD
`
`Lubrifair
`
`Testosterone EPD
`
`Profiderall
`
`PR
`
`Testoderm
`
`EPD
`
`TechneScan
`and
`
`TechneScan
`
`EPD
`
`Terfenadine
`
`EPD
`
`Barbidonna
`
`PR
`
`Fastlene
`
`Zaditor
`
`EPD
`
`EPD
`
`Trifedrine
`
`PR
`
`Tibolone
`
`Zoladex
`
`(m4)
`
`EPD
`
`EPD
`
`PR
`
`mofiban
`
`MDP
`Em ___-
`
`Look and Sound Similar
`
`Name
`
`Source
`
`Name
`
`Source
`
`Name
`
`Source
`
`Our analysis of the 38 names contained in Table 1 considered the information obtained in
`the previous sections along with their product characteristics. We determined all 38
`names do not pose a risk for confusion as described in Appendices D through E.
`
`2.2.6 Failure Mode and Effects Analysis ofModifier
`
`As proposed, the Applicant does not include a modifier with the name (e.g., EC, En-tabs)
`to convey that Tecfidera is a delayed—release dosage form. Tecfidera is a new molecular
`entity in which there is no immediate-release dosage form available.
`
`a:
`
`. This document contains proprietary and confidential infatuation that should not be released to the public.
`
`Reference ID: 3246593
`
`4
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`

`
`
`We evaluated whether the lack of modifier raises a potential safety concern, specifically
`if practitioners or patients were to assume that Tecfidera is an immediate-release dosage
`form because no modifier is present in the proprietary name to signal the delayed-release
`nature of the product. Therefore, we evaluated errors associated with currently marketed
`products to consider whether a modifier may be appropriate for this drug to convey the
`delayed-release properties of this product.
`First, we identified delayed-release products approved without a modifier in the
`proprietary name and reviewed documented errors relating to wrong technique. Wrong
`technique errors involved patients or practitioners, chewing, splitting, opening, or
`crushing the delayed-release oral dosage forms when these products were intended to be
`administered intact. Wrong technique errors occurred despite the presence of clear
`labeling directives to administer the products intact.
`We then considered whether the lack of a modifier may actually contribute to
`practitioners’ and patients’ knowledge deficit about the delayed-release properties of the
`drug product. As it relates to this product, this consideration led us to evaluate whether
`the addition of a modifier to the Tecfidera name might help to avoid some of the wrong
`technique errors.
`We reviewed the Institute for Safe Medication Practices’ (ISMP) list of “Oral Dosage
`Forms That Should Not Be Crushed” to identify if a modifier exists that could possibly
`convey that a delayed-release dosage form cannot be manipulated or that conveys the
`frequency of administration associated with a delayed-release dosage form. We focused
`our review on those names with modifiers for delayed-release products (e.g. EC, En-
`tabs), since the Institute of Medicine has charged FDA and Industry to standardize
`abbreviations to the greatest extent possible. Our review found that this list contains a
`majority of proprietary names without a modifier (n = 17) versus proprietary names with
`a modifier (n = 3). Based on this information, we conclude that there is no standard
`single modifier currently on the market today that is definitively linked to the
`requirement that a delayed-release product should not be manipulated prior to
`administration. Additionally, the frequency of administration for currently marketed
`delayed-release dosage forms vary from once daily to four times daily to once weekly.
`Based on this information, there is insufficient evidence to conclude that a modifier can
`convey the delayed-release properties of a product to prevent wrong technique errors or
`wrong frequency of administration errors. Additionally, there is also no currently
`marketed immediate-release dosage form of this product that the proposed product would
`need to distinguish itself from.
`Given the totality of the factors considered above, there is no compelling evidence to
`support the necessity to request a modifier for the proposed proprietary name, Tecfidera,
`at this time. If approved, DMEPA will monitor for medication errors where the
`proprietary name is a contributing factor to the error.
`
`2.2.7 Communication of DMEPA’s Final Decision to Other Disciplines
`DMEPA communicated our findings to the Division of Neurology Products (DNP) via e-
`mail on December 26, 2012. At that time we also requested additional information or
`concerns that could inform our review. Per e-mail correspondence from DNP on
`
`Reference ID: 3246593
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`

`
`
`December 26, 2012, a reviewer stated that the proposed proprietary name Tecfidera
`looked similar to the name, Terfenadine. The name Terfenadine was also identified by
`EPD and was evaluated in Appendix E and found not to pose a risk for confusion.
`
`CONCLUSIONS
`3
`The proposed proprietary name is acceptable from both a promotional and safety
`perspective.
`If you have further questions or need clarifications, please contact Laurie Kelley, OSE
`project manager, at 301-796-5068.
`
`COMMENTS TO THE APPLICANT
`3.1
`We have completed our review of the proposed proprietary name, Tecfidera, and have
`concluded that this name is acceptable. However, if any of the proposed product
`characteristics as stated in your October 24, 2012 submission are altered, the name must
`be resubmitted for review.
`
`
`
`
`
`
`
`
`
`
`
`
`
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`
`
`
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`
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`Reference ID: 3246593
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`
`4
`
`REFERENCES
`
`1. Micromedex Integrated Index (http://csi.micromedex.com)
`Micromedex contains a variety of databases covering pharmacology, therapeutics,
`toxicology and diagnostics.
`
`2. Phonetic and Orthographic Computer Analysis (POCA)
`POCA is a database which was created for the Division of Medication Error
`Prevention and Analysis, FDA. As part of the name similarity assessment, proposed
`names are evaluated via a phonetic/orthographic algorithm. The proposed proprietary
`name is converted into its phonemic representation before it runs through the phonetic
`algorithm. Likewise, an orthographic algorithm exists which operates in a similar
`fashion.
`
`3. Drug Facts and Comparisons, online version, St. Louis, MO
`(http://factsandcomparisons.com)
`Drug Facts and Comparisons is a compendium organized by therapeutic course; it
`contains monographs on prescription and OTC drugs, with charts comparing similar
`products. This database also lists the orphan drugs.
`
`4. FDA Document Archiving, Reporting & Regulatory Tracking System [DARRTS]
`DARRTS is a government database used to organize Applicant and Sponsor
`submissions as well as to store and organize assignments, reviews, and
`communications from the review divisions.
`
`5. Division of Medication Errors Prevention and Analysis proprietary name
`consultation requests
`This is a list of proposed and pending names that is generated by the Division of
`Medication Error Prevention and Analysis from the Access database/tracking system.
`
`6. Drugs@FDA (http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm)
`Drugs@FDA contains most of the drug products approved since 1939. The majority of
`labels, approval letters, reviews, and other information are available for drug products
`approved from 1998 to the present. Drugs@FDA contains official information about FDA
`approved brand name, generic drugs, therapeutic biological products, prescription and over-
`the-counter human drugs and discontinued drugs and “Chemical Type 6” approvals.
`7. U.S. Patent and Trademark Office (http://www.uspto.gov)
`USPTO provides information regarding patent and trademarks.
`
`8. Clinical Pharmacology Online (www.clinicalpharmacology-ip.com)
`Clinical Pharmacology contains full monographs for the most common drugs in
`clinical use, plus mini monographs covering investigational, less common,
`combination, nutraceutical and nutritional products. It also provides a keyword
`search engine.
`
`Reference ID: 3246593
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`
`
`9. Data provided by Thomson & Thomson’s SAEGIS ™ Online Service, available at
`(www.thomson-thomson.com)
`The Pharma In-Use Search database contains over 400,000 unique pharmaceutical
`trademarks and trade names that are used in about 50 countries worldwide. The data
`is provided under license by IMS HEALTH.
`
`10. Natural Medicines Comprehensive Databases (www.naturaldatabase.com)
`Natural Medicines contains up-to-date clinical data on the natural medicines, herbal
`medicines, and dietary supplements used in the western world.
`
`11. Access Medicine (www.accessmedicine.com)
`Access Medicine® from McGraw-Hill contains full-text information from
`approximately 60 titles; it includes tables and references. Among the titles are:
`Harrison’s Principles of Internal Medicine, Basic & Clinical Pharmacology, and
`Goodman and Gilman’s The Pharmacologic Basis of Therapeutics.
`
`12. USAN Stems (http://www.ama-assn.org/ama/pub/about-ama/our-people/coalitions-
`consortiums/united-states-adopted-names-council/naming-guidelines/approved-
`stems.shtml)
`USAN Stems List contains all the recognized USAN stems.
`
`13. Red Book (www.thomsonhc.com/home/dispatch)
`Red Book contains prices and product information for prescription, over-the-counter
`drugs, medical devices, and accessories.
`
`14. Lexi-Comp (www.lexi.com)
`Lexi-Comp is a web-based searchable version of the Drug Information Handbook.
`
`15. Medical Abbreviations (www.medilexicon.com)
`Medical Abbreviations dictionary contains commonly used medical abbreviations and
`their definitions.
`
`16. CVS/Pharmacy (www.CVS.com)
`This database contains commonly used over the counter products not usually
`identified in other databases.
`
`17. Walgreens (www.walgreens.com)
`This database contains commonly used over the counter products not usually
`identified in other databases.
`
`18. Rx List (www.rxlist.com)
`RxList is an online medical resource dedicated to offering detailed and current
`pharmaceutical information on brand and generic drugs.
`
`Reference ID: 3246593
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`
`
`19. Dogpile (www.dogpile.com)
`Dogpile is a Metasearch engine that searches multiple search engines including
`Google, Yahoo! and Bing, and returns the most relevant results to the search.
`
`20. Natural Standard (http://www.naturalstandard.com)
`Natural Standard is a resource that aggregates and synthesizes data on complementary
`and alternative medicine.
`
`Reference ID: 3246593
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`

`
`
`APPENDICES
`Appendix A
`FDA’s Proprietary Name Risk Assessment considers the promotional and safety aspects
`of a proposed proprietary name. The promotional review of the proposed name is
`conducted by OPDP. OPDP evaluates proposed proprietary names to determine if they
`are overly fanciful, so as to misleadingly imply unique effectiveness or composition, as
`well as to assess whether they contribute to overstatement of product efficacy,
`minimization of risk, broadening of product indications, or making of unsubstantiated
`superiority claims. OPDP provides their opinion to DMEPA for consideration in the
`overall acceptability of the proposed proprietary name.
`The safety assessment is conducted by DMEPA. DMEPA staff search a standard set of
`databases and information sources to identify names that are similar in pronunciation,
`spelling, and orthographically similar when scripted to the proposed proprietary name.
`Additionally, we consider inclusion of USAN stems or other characteristics that when
`incorporated into a proprietary name may cause or contribute to medication errors (i.e.,
`dosing interval, dosage form/route of administration, medical or product name
`abbreviations, names that include or suggest the composition of the drug product, etc.).
`DMEPA defines a medication error as any preventable event that may cause or lead to
`inappropriate medication use or patient harm while the medication is in the control of the
`health care professional, patient, or consumer. 1
`Following the preliminary screening of the proposed proprietary name, DMEPA gathers
`to discuss their professional opinions on the safety of the proposed proprietary name.
`This meeting is commonly referred to the Center for Drug Evaluation and Research
`(CDER) Expert Panel discussion. DMEPA also considers other aspects of the name that
`may be misleading from a safety perspective. DMEPA staff conducts a prescription
`simulation studies using FDA health care professionals. When provided, DMEPA
`considers external proprietary name studies conducted by or for the Applicant/Sponsor
`and incorporates the findings of these studies into the overall risk assessment.
`The DMEPA primary reviewer assigned to evaluate the proposed proprietary name is
`responsible for considering the collective findings, and provides an overall risk
`assessment of the proposed proprietary name. DMEPA bases the overall risk assessment
`on the findings of a Failure Mode and Effects Analysis (FMEA) of the proprietary name
`and misleading nature of the proposed proprietary name with a focus on the avoidance of
`medication errors.
`DMEPA uses the clinical expertise of its staff to anticipate the conditions of the clinical
`setting where the product is likely to be used based on the characteristics of the proposed
`product. DMEPA considers the product characteristics associated with the proposed
`product throughout the risk assessment because the product characteristics of the
`proposed may provide a context for communication of the drug name and ultimately
`determine the use of the product in the usual clinical practice setting.
`
`
`1 National Coordinating Council for Medication Error Reporting and Prevention. http://www.nccmerp.org/aboutMedErrors.html.
`Last accessed 10/11/2007.
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`
`
`Typical product characteristics considered when identifying drug names that could
`potentially be confused with the proposed proprietary name include, but are not limited
`to; established name of the proposed product, proposed indication of use, dosage form,
`route of administration, strength, unit of measure, dosage units, recommended dose,
`typical quantity or volume, frequency of administration, product packaging, storage
`conditions, patient population, and prescriber population. DMEPA considers how these
`product characteristics may or may not be present in communicating a product name
`throughout the medication use system. Because drug name confusion can occur at any
`point in the medication use process, DMEPA considers the potential for confusion
`throughout the entire U.S. medication use process, including drug procurement,
`prescribing and ordering, dispensing, administration, and monitoring the impact of the
`medication.2
`The DMEPA considers the spelling of the name, pronunciation of the name when spoken, and
`appearance of the name when scripted. DMEPA compares the proposed proprietary name
`with the proprietary and established name of existing and proposed drug products and names
`currently under review at the FDA. DMEPA compares the pronunciation of the proposed
`proprietary name with the pronunciation of other drug names because verbal communication
`of medication names is common in clinical settings. DMEPA examines the phonetic
`similarity using patterns of speech. If provided, DMEPA will consider the Sponsor’s intended
`pronunciation of the proprietary name. However, DMEPA also considers a variety of
`pronunciations that could occur in the English language because the Sponsor has little control
`over how the name will be spoken in clinical practice. The orthographic appearance of the
`proposed name is evaluated using a number of different handwriting samples. DMEPA
`applies expertise gained from root-cause analysis of postmarketing medication errors to
`identify sources of ambiguity within the name that could be introduced when scripting
`(e.g.,“T” may look like “F,” lower case ‘a’ looks like a lower case ‘u,’ etc). Additionally,
`other orthographic attributes that determine the overall appearance of the drug name when
`scripted (see Table 1 below for details).
`
`
`
`
`
`
`
`
`
`
`2 Institute of Medicine. Preventing Medication Errors. The National Academies Press: Washington DC. 2006.
`
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`
`
`Table 1. Criteria Used to Identify Drug Names that Look- or Sound-Similar to a
`Proposed Proprietary Name.
`
`Considerations when Searching the Databases
`
`Attributes Examined to Identify
`Similar Drug Names
`
`Potential Effects
`
`Potential
`Causes of Drug
`Name
`Similarity
`
`Similar spelling
`
`
`Type of
`Similarity
`
`
`
`
`
`
`Look-
`alike
`
`Orthographic
`similarity
`
`Identical prefix
`Identical infix
`Identical suffix
`Length of the name
`Overlapping product
`characteristics
`
`• Names may appear similar
`in print or electronic media
`and lead to drug name
`confusion in printed or
`electronic communication
`• Names may look similar
`when scripted and lead to
`drug name confusion in
`written communication
`• Names may look similar
`when scripted, and lead to
`drug name confusion in
`written communication
`
`Similar spelling
`Length of the name/Similar
`shape
`Upstrokes
`Down strokes
`Cross-strokes
`Dotted letters
`Ambiguity introduced by
`scripting letters
`Overlapping product
`characteristics
`Identical prefix
`Identical infix
`Identical suffix
`Number of syllables
`Stresses
`Placement of vowel sounds
`Placement of consonant sounds
`Overlapping product
`characteristics
`Lastly, DMEPA considers the potential for the proposed proprietary name to
`inadvertently function as a source of error for reasons other than name confusion. Post-
`marketing experience has demonstrated that proprietary names (or components of the
`proprietary name) can be a source of error in a variety of ways. Consequently, DMEPA
`considers and evaluates these broader safety implications of the name throughout this
`assessment and the medication error staff provides additional comments related to the
`
`Sound-
`alike
`
`Phonetic
`similarity
`
`
`• Names may sound similar
`when pronounced and lead
`to drug name confusion in
`verbal communication
`
`Reference ID: 3246593
`
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`safety of the proposed proprietary name or product based on professional experience with
`medication errors.
`
`1. Database and Information Sources
`DMEPA searches the internet, several standard published drug product reference texts,
`and FDA databases to identify existing and proposed drug names that may sound-alike or
`look-alike to the proposed proprietary name. A standard description of the databases
`used in the searches is provided in the reference section of this review. To complement
`the process, the DMEPA uses a computerized method of identifying phonetic and
`orthographic similarity between medication names. The program, Phonetic and
`Orthographic Computer Analysis (POCA), uses complex algorithms to select a list of
`names from a database that have some similarity (phonetic, orthographic, or both) to the
`trademark being evaluated. Lastly, DMEPA reviews the USAN stem list to determine if
`any USAN stems are present within the proprietary name. The individual findings of
`multiple safety evaluators are pooled and presented to the CDER Expert Panel. DMEPA
`also evaluates if there are characteristics included in the composition that may render the
`name unacceptable from a safety perspective (abbreviation, dosing interval, etc.).
`
`2. Expert Panel Discussion
`DMEPA gathers gather CDER professional opinions on the safety of the proposed
`product and discussed the proposed proprietary name (Expert Panel Discussion). The
`Expert Panel is composed of Division of Medication Errors Prevention (DMEPA) staff
`and representatives from the Office of Prescription Drug Promotion (OPDP). We also
`consider input from other review disciplines (OND, ONDQA/OBP). The Expert Panel
`also discusses potential concerns regarding drug marketing and promotion related to the
`proposed names.
`The primary Safety Evaluator presents the pooled results of the database and information
`searches to the Expert Panel for consideration. Based on the clinical and professional
`experiences of the Expert Panel members, the Panel may recommend additional names,
`additional searches by the primary Safety Evaluator to supplement the pooled results, or
`general advice to consider when reviewing the proposed proprietary name.
`
`3. FDA Prescription Simulation Studies
`Three separate studies are conducted within the Centers of the FDA for the proposed
`proprietary name to determine the degree of confusion of the proposed proprietary name
`with marketed U.S. drug names (proprietary and established) due to similarity in visual
`appearance with handwritten prescriptions or verbal pronunciation of the drug name. The
`studies employ healthcare professionals (pharmacists, physicians, and nurses), and
`attempts to simulate the prescription ordering process. The primary Safety Evaluator
`uses the results to identify orthographic or phonetic vulnerability of the proposed name to
`be misinterpreted by healthcare practitioners.
`In order to evaluate the potential for misinterpretation of the proposed proprietary name
`in handwriting and verbal communication of the name, inpatient medication orders and/or
`outpatient prescriptions are written, each consisting of a combination of marketed and
`unapproved drug products, including the proposed name. These orders are optically
`
`Reference ID: 3246593
`
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`
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`scanned and one prescription is delivered to a random sample of participating health
`professionals via e-mail. In addition, a verbal prescription is recorded on voice mail.
`The voice mail messages are then sent to a random sample of the participating health
`professionals for their interpretations and review. After receiving either the written or
`verbal prescription orders, the participants record their interpretations of the orders which
`are recorded electronically.
`
`4. Comments from Other Review Disciplines
`DMEPA requests the Office of New Drugs (OND) and/or Office of Generic Drugs
`(OGD), ONDQA or OBP for their comments or concerns with the proposed proprietary
`name, ask for any clinical issues that may impact the DMEPA review during the initial
`phase of the name review. Additionally, when applicable, at the same time DMEPA
`requests concurrence/non-concurrence with OPDP’s decision on the name. The primary
`Safety Evaluator addresses any comments or concerns in the safety evaluator’s
`assessment.
`
`The OND/OGD Regulatory Division is contacted a second time following our analysis of
`the proposed proprietary name. At this point, DMEPA conveys their decision to accept
`or reject the name. The OND or OGD Regulatory Division is requested to provide any
`further information that might inform DMEPA’s final decision on the proposed name.
`Additionally, other review disciplines opinions such as ONDQA or OBP may be
`considered depending on the proposed proprietary name.
`
`5. Safety Evaluator Risk Assessment of the Proposed Proprietary Name
`The primary Safety Evaluator applies his/her individual expertise gained from evaluating
`medication errors reported to FDA, considers all aspects of the name that may be
`misleading or confusing, conducts a Failure Mode and Effects Analysis, and provides an
`overall decision on acceptability dependent on their risk